In October 2011, the BMJ published a randomised controlled trial on the effect of tranexamic acid on blood transfusion in patients undergoing radical retropubic prostatectomy. The authors pointed out that this was the first trial to assess the effect of tranexamic acid on blood transfusion in this particular operation. 

While this may be the case, it was not the first trial to examine the effect of tranexamic acid on blood transfusion in surgery more generally. A systematic review published in 2001 presented data from 18 clinical trials and showed that tranexamic acid reduces the probability of blood transfusion in elective surgery by 34%.

Ker et al, based in the London School of Hygiene and Tropical Medicine, assessed the current evidence for the effect of tranexamic acid on blood transfusion, thromboembolic events, and mortality in surgical patients.¹ To examine how the evidence has changed over time they performed a systematic review using cumulative meta-analyses.

Study selection specified randomised controlled trials that compared tranexamic acid with no tranexamic acid or placebo in elective and emergency surgery. No age restriction was applied. 

Potentially eligible trials were identified by searching the Cochrane central register of controlled trials (2011, issue 3), Medline (1950 to September 2011), and Embase (1980 to September 2011). The authors used a combination of subject headings and text words to identify randomised controlled trials of any anti-fibrinolytic drug. Searches were not restricted by language or publication status. 

To identify ongoing or unpublished trials the WHO International Clinical Trials Registry Platform was also used. 

Two authors independently screened the search output to identify records of potentially eligible trials, the full texts of which were retrieved and assessed for inclusion. The outcome measures of interest were:

• The number of patients receiving a blood transfusion
• The number of patients with a thromboembolic event (myocardial infarction [MI], stroke, deep vein thrombosis [DVT] and pulmonary embolism [PE])
• The number of deaths. 

The trial authors say the results of the 129 trials, totalling 10,488 patients, carried out between 1972 and 2011, were included. Tranexamic acid reduced the probability of receiving a blood transfusion by a third (risk ratio 0.62, 95% confidence interval 0.58 to 0.65; p < 0.001). This effect remained when the analysis was restricted to trials using adequate allocation concealment (0.68, 0.62 to 0.74; p < 0.001). The effect of tranexamic acid was uncertain on:

• MI (0.68, 0.43 to 1.09; p = 0.11)
• Stroke (1.14, 0.65 to 2.00; p = 0.65)
• DVT (0.86, 0.53 to 1.39; p = 0.54)
• PE (0.61, 0.25 to 1.47; p = 0.27).

Fewer deaths occurred in the tranexamic acid group (0.61, 0.38 to 0.98; p = 0.04), although when the analysis was restricted to trials using adequate concealment there was considerable uncertainty (0.67, 0.33 to 1.34; p = 0.25). 

Cumulative meta-analysis showed that reliable evidence that tranexamic acid reduces the need for transfusion has been available for over 10 years.

Strong evidence that tranexamic acid reduces blood transfusion in surgery has been available for many years. Further trials on the effect of tranexamic acid on blood transfusion are unlikely to add useful new information. 

However, the effect of tranexamic acid on thromboembolic events and mortality remains uncertain. Surgical patients should be made aware of this evidence so that they can make an informed choice.

Reference

1. Ker K, Edwards P, Perel P et al, BMJ 2012; 344: e3054